week 6- rates patterns

Question 1

why study rates of evolution

Answer 1

-key in molecular evolution how fast DNA sequences evolve
-rates amoung different genetic (codons) and nongeneic regions differ
-understand evolutionary forces responsible for variable rates and patterns of evolution. = functional constraint, positive selection, mutation input

Question 2

what is the rate of point mutation

Answer 2

ultimate source of novelty
number of new sequence variants in a target sequence per unit time

Question 3

what is a target sequence

Answer 3

nucleotide, gene, chromosome, genome

Question 4

what is unit time

Answer 4

replication, generations, chronological time

Question 5

why is rate of point mutation difficult to measure

Answer 5

mutations are unpredictable and often deleterious and lethal

Question 6

how to calculate rate of mutations of the deleterious alleles

Answer 6

if you know frequency of mutant and the selection coefficient against that mutant then you can calculate this

q=u/s
q= frequency, u is mutation rate, and s is selection coefficient

Question 7

what does neutral mutation rate equal and how to work out

Answer 7

substitution for neutral alleles
use non-functional DNA and homologous DNA sequences between two species with known divergence time (e.g. from fossils) and generation times

Question 8

human and chimpanzee: non-genic regions

Answer 8

2x10-8 per nucleotide per generation
multiplying this with human genome size of 7x109:
100 new point mutations per baby

Question 9

explain the direct method

Answer 9

compare non-recombining DNA of two individuals with known generations apart
Rates vary across the genome

Question 10

what is rate of substitution

Answer 10

how long does it take for all individuals of a species to have that particular mutation

Question 11

equation for rate of nucleotide substitution

Answer 11

r = K/2T
r is number of substitutions per site per year
K is number of substitutions betwween two sequences
T is time of divergence

Question 12

what is a non-synonymous rate

Answer 12

approx. 300 fold diffference between genes
-very conservative: core histones H3 and H4: practically zero
-interferon y: 3.1x 10-9 years

Question 13

what is a synonomous rate

Answer 13

varies across gene but much smaller standard variation
-logical that synonomous substitutions are more frequent as those substitutions do not lead to a different amino acid in the protein, hence less/no purifying selection

Question 14

is synonymous or non-synonymous faster rate of evolution

Answer 14

synonymous about 5 times faster

Question 15

relative rate of evolution letters explained

Answer 15

-dN is number of non-synonymous substitutions per non-synonymous site
-dS is number of synonymous substitutions per synonymous site
-dN/dS ratio also called lower case omega (interchangeable with KA/KS)

Question 16

what is directional pattern

Answer 16

we know which one is the original e.g. A->T

Question 17

what is nondirectinal

Answer 17

we do not know which direction e.g. A <-> T

Question 18

how to work out direction of mutation

Answer 18

need to use an outgroup to know direction, use a pseudogene as compared to its functional counterpart

Question 19

how many possible changes

Answer 19

12 possible changes: matrix: relative frequency in which a change occurs

Question 20

what are substitution matrices used for

Answer 20

to calculate distances between sequences and build phylogenetic trees

Question 21

what can different models of substitution rates be used fir

Answer 21

can be used when building a phylogeny to understand which substitutions are more likely

Question 22

what are all synonymous mutations

Answer 22

assumed to be selectively neutral

Question 23

what can nonsynonymous mutations be

Answer 23

advantageous, neutral or disadvantageous, suggestive of selection

Question 24

what do nonsynonymous nutations that are advantageous undergo

Answer 24

undergo fixation faster than neutral

Question 25

if dN/dS >1

Answer 25

positive selection

Question 26

if dN/dS = 1

Answer 26

strictly neutral (is it a functional gene)

Question 27

if dN/dS <1

Answer 27

only drift and negative or purifying selection act

Question 28

what does high dN =

Answer 28

positive selection

Question 29

what does low dN =

Answer 29

purifying selection

Question 30

is positive selection or purifying selection common

Answer 30

purifying positive is rare

Question 31

how to calculate dN/dS

Answer 31

need 2 DNA sequences so you can identify mutant sites -ancestral sequence or outgroup need to translate into amino acids to see if mutation in the codons lead to a different a.a. need to determine how many sites could be synonymous or non-synonymous if they mutated then calculate dN as number of nonsynonymous mutations/total nonsynonymous sites and dS accordingly

Question 32

What is the molecular clock

Answer 32

the hypothesis that DNA sequences accumulate changes at a constant rate through time provides a simple yet powerful way of dating evolutionary events

Question 33

as a result opf the molecular clock what is the number of differences in a DNA sequence between two organisms proportional to

Answer 33

the time since divergence

Question 34

why is the molecular clock called that

Answer 34

although substitutions occur at random times the rate at which they occur is assumed to be constant or 'clocklike' through time and across lineages

Question 35

what does the molecular clock allow you to calculate

Answer 35

divergence times for other species

Question 36

molecular clock controversy

Answer 36

the clock is 'sloppy' woth variable 'tick rate' The result is large confidence intervals on date estimates

Question 37

explain mitochondrial DNA rates

Answer 37

Mt coding genes much higher synonymous rates than nucler coding DNA rate of mutation higher

Question 38

because Mt rate of mutation is higher what does that mean

Answer 38

low fidelity of replication, inefficient repair, high concentration of mutagens, effective population size 1/4 of that of nuclear genes

Question 39

in plants and fungi at what rate do Mt evolve

Answer 39

very slowly but with some exceptional taxa

Question 40

explain chloroplast DNA evolution

Answer 40

150000 bp long (50 -250 kb) conserved in gene order and content in photosynthetic plants: dN/dS<1 in non-photosynthetic plants (parasites): dN/dS > 1

Question 41

explain virus evolution

Answer 41

evolve extremely fast (1 million times faster than animal DNA) serially sample viruses can be studied easily KA/KS< 1, but purifying selection is weaker than in animal genes errors in reverse transcription RNa to DNA rapid rate changes properties, such as antigenicity high error rate is actually an advantage: evolution of evolvability

Question 42

what is coalescence

Answer 42

theory that allows estimation of population size in the past looks for most common ancestor (MRCA) how fast this goes is effected by population size, drift, selection, migration etc relationship of all alleles: gene genealogy (or coalescent)

Question 43

what do retrospective models of population genetics show

Answer 43

trace all alleles of a gene in a population to a single ancestral copy

Question 44

what is coalescent theory a model of

Answer 44

how alleles sampled from a population may have originated from a common ancestor

Question 45

what is the rate of coalescence impacted by

Answer 45

effective population size , mutation rate, other evolutionary processes

Question 46

what is MSMC analysis

Answer 46

multiple sequenctially markocian coalescent. could be used to estimate the demographic history of a population using whole genome sequences and coalescnet theory